【作者】 刘新林；

【导师】 李玉明；

【作者基本信息】 天津医科大学 ， 内科学， 2007， 硕士

【摘要】 目的：急性冠脉综合征(Acute Coronary Syndrome，ACS)是冠心病(Coronary Heart Disease，CHD)的最常见类型，包括不稳定型心绞痛(Unstable Angina Pectoris，UAP)、非ST段抬高型心肌梗死(non ST segment Elevation Myocardial Infarction，NSTE-MI)、ST段抬高型心肌梗死(ST segment Elevation Myocardial Infarction，STE-MI)，三者在ACS中所占比例分别为12.86％，66.14％，21.00％。其中UAP和NSTE-MI又被称为非ST段抬高型急性冠脉综合征(non ST segment Elevation Acute Coronary Syndrome，NSTE-ACS)，斑块破裂诱发非闭塞性血栓形成是NSTE-ACS的主要发病机制。UAP预后变化不定，可发展成急性心肌梗死(Acute Myocardial Infarction，AMI)，也可转变为稳定型心绞痛(Stable Angina Pectoris，SAP)。如何在发病早期评价其发生心脏事件的危险性并及时给予正确干预，对改善疾病预后至关重要。心肌损伤标志物的检测对于ACS患者早期诊断、危险分层及处理具有重要的作用，目前临床中主要应用心肌型肌酸激酶同工酶(MB Isotype of Creatine Kinase，CK-MB)和心脏肌钙蛋白Ⅰ(Cardiac Troponin I，cTnI)联合检测的方法。本研究通过对NSTE-ACS患者入院早期(＜48h)冠脉造影检查和CK-MB、cTnI的检测结果进行分析，探讨这些患者的临床特征及CK-MB、cTnI结果特点，评价CK-MB、cTnI在NSTE-ACS患者早期危险分层及处理中的作用，力求为临床中更加合理有效应用CK-MB、cTnI联合检测方法提供依据。方法：检索2004年4月-2007年1月在武警医学院附属医院心内科住院治疗的患者病历，采用回顾性研究的方法，连续入选1074例NSTE-ACS患者，分析入院早期(＜48h)冠脉造影结果，并采集症状发作至入院36h内cTnI和CK-MB检测值。以＞正常值上限(Upper Limits of Normal，ULN)作为阳性结果，以≤ULN作为阴性结果，据此：1．将入选患者分为4组：所有标志物阴性组(CK-MB~-／cTnI~-)，CK-MB阳性和cTnI阴性组(CK-MB~+／cTnI~-)，CK-MB阴性和cTnI阳性组(CK-MB~-／cTnI~+)，所有标志物阳性组(CK-MB~+／cTnI~+)。评价组间结果一致与不一致的发生率及早期侵入性检查(＜48h)应用情况，统计各组院内主要不良心脏事件(Major Adverse Cardiac Event，MACE)。2．据cTnI是否阳性，将患者分为cTnI~+组和cTnI~-组，再次比较患者基本临床资料及冠脉造影、MACE，评价cTnI在NSTE-ACS患者危险分层中的作用。3．据CK-MB是否阳性，对患者上述资料进行比较，评价CK-MB在NSTE-ACS患者危险分层中的作用，同时比较cTnI和CK-MB对NSTE-ACS危险分层的作用。4．比较CK-MB~+／cTnI~-和CK-MB~-／cTnI~+两组间资料特征，评价这两组对NSTE-ACS危险分层的作用。5．去除所有肾功能异常患者(Cr＞132μmol／L)，再次评价四组间基本资料，明确轻度肾功能异常对心肌损伤标志物的影响。结果：1．在最初纳入统计的1074名患者中，cTnI~+318人，CK-MB~+356人。两种标志物检测结果一致者共930人，其中CK-MB~-／cTnI~-664人(61.82％)，CK-MB~+／cTnI~+患者266人(24.77％)。13.41％的患者CK-MB和cTnI结果不一致(n=90[8.38％]CK-MB~+／cTnI~-；n=54[5.03％]CK-MB／cTnI~+)。2．在不考虑CK-MB情况下，cTnI~+组较cTnI~-组卒中史发生率(P=0.008)、尿蛋白阳性率(P=0.006)、白细胞(White Blood Corpuscle，WBC)计数异常比例(P=0.01)、冠脉病变支数(2支P=0.018；3支P=0.002)、冠脉病变心血管造影和介入治疗学会分型(Society forCardiac Angiography and Interventions，SCAI)Ⅱ型(P＜0.001)、Ⅲ型(P=0.001)、Ⅳ型(P＜0.001)病变发生率增多；左室射血分数(Left Ventricular Ejection Fraction，LVEF)值低(P=0.005)；MACE发生率增加P＜0.001)。3．在不考虑cTnI的情况下，CK-MB~+组较CK-MB~-组男性比例(P=0.028)、高血压(P=0.001)、尿蛋白阳性(P＜0.001)、中风史(P=0.008)、冠脉病变支数(2支P=0.018；3支P=0.004)、冠脉病变SCAI分型Ⅲ型(P=0.004)、Ⅳ型(P＜0.001)病变增多；LVEF值低(P=0.033)；院内MACE发生率无统计学差异(P=0.201)。4．CK-MB~-／cTnI~+与CK-MB~+／cTnI~-两组间各指标比较无统计学差异。5．无论是单独以cTnI作为标志物(cTnI~+组与cTnI~-组比较P=0.001)还是单独以CK-MB作为标志物(CK-MB~+组与CK-MB~-组比较P=0.003)，WBC计数异常比例在阳性组与阴性组间均存在统计学差异。结论：1．在NSTE-ACS患者中，cTnI升高能够独立预测患者预后。2．据入院时检测结果单独CK-MB~+预测价值与单独cTnI~+比较无明显差异。3．cTnI既是一种心肌细胞损伤标志物，也是反映左室收缩功能受损程度的指标。4．入院cTnI~+的患者较cTnI~-患者冠脉造影示冠脉病变重，院内MACE增多。5．尿蛋白异常与NSTE-ACS患者cTnI升高有一定联系。轻度肾功能损害时，cTnI对NSTE-ACS患者预后判断的价值不受影响。6．WBC计数对NSTE-ACS患者危险分层具有一定临床参考价值。更多还原

【Abstract】 ObjectiveACS (Acute Coronary Syndrome) is an important subtype of CHD(Coronary Heart Disease). It is composed of UAP (Unstable AnginaPectoris), NSTE-MI (non ST segment Elevation Myocardial Infarction),and STE-MI (ST segment Elevation Myocardial Infarction), and theproportion of each component is 12.86%, 66.14%, 21.00% respectively.UAP and NSTE-MI are also called NSTE-ACS (non ST segment ElevationAcute Coronary Syndrome). The main mechanism of ACS is rupture orerosion of the unstable atherosclerotic plaque and thereby incompleteocclusion of the coronary artery by thrombosis. The pathologicalevolution of UAP is uncertain, which can either develop into AMI or runto stable angina pectoris (SAP). Evaluation of the risks in ACS patientsand early initiation of proper therapy is very important for ameliorationof clinical outcome. The purpose of present study is to evaluate theassociation between markers of cardiac injury and early coronaryangiography results, in-hospital myocardial infarction, cardiac death,revascularization and treatment patterns in patients with NSTE-ACS, andto provide a rationale for the interpretation of double detection of cardiacbiomarkers in clinical settings.Methods1074 NSTE-ACS patients admitted in the division of cardiology,Medical College Affiliated Hospital of Chinese People’s Armed PoliceForces (CPAPF) during Apr, 2004～Jul 2007, whose CK-MB and cTnI were measured within the first 36 hours from symptom onset afteradmission, were enrolled in the present study. All patients receivedcoronary angiography within 48h. Positive results were recorded ifbiomarker＞1×upper limit of normal (ULN), and negative result wasrecorded when biomarker≤1×ULN.1. We examined relationships between results of four markercombinations (CK-MB~-/cTnI~-, CK-MB~+/cTnI~-, CK-MB~-/cTnI~+, andCK-MB~+/cTnI~+) and incidences of in-hospital myocardial infarction,cardiac death and early catheter-based interventions.2. All patients were assigned to cTnI~+ group and cTnI~- groupaccording to level of cTnI. We examined the relationships between cTnIlevel with demographic and clinical data and incidence of in-hospitalmyocardial infarction, cardiac death and early catheter-basedinterventions.3. All patients were re-analyzed according to the results of CK-MB.4. We analyzed the data in CK-MB~+/cTnI~- group and CK-MB~-/cTnI~+group, and evaluated their roles in risk stratification of NSTE-ACS.5. In another subset of analysis, patients with renal dysfunction(Cr＞132μmol/L) were all excluded. Then we reevaluated the data in fourgroups, in order to identify the impact of slight renal functioninsufficiency on the level of cardiac biomarkers.Results1. Among 1074 NSTE-ACS patients, 318 were cTnI~+, and 356 wereCK-MB~+. Results from 930 patients were accordant in CK-MB and cTnIlevel, and the other 144 were discordant (n=90 [8.38%] CK-MB~+/cTnI~-;n=54 [5.03%] CK-MB~-/cTnI~+).2. The incidences of stroke(P=0.008), proteinuria(P=0.006),WBC(White Blood Corpuscle)count(P=0.01), number of damagedcoronary artery(2, P=0.018; 3, P=0.002), SCAI(Society for CardiacAngiography and Interventions)typeⅡ(P＜0.001),Ⅲ(P=0.001) and Ⅳ(P＜0.001) coronary artery damage and MACE (Main Adverse CardiacEvent) were higher in cTnI~+ group regardless the level of CK-MB.3. Except for the incidence of MACE (P=0.201), similarly resultswere observed from CK-MB group regardless the level of cTnI.4. The number and types of damaged coronary artery and theincidence of MACE did not have statistical difference between theCK-MB~-/cTnI~+ and CK-MB~+/cTnI~- group.5. WBC count was found effective in risk stratification, whetherpatients were grouped by cTnI or by CK-MB.Conclusions1. Elevation of cTnI alone can predict a higher risk of NSTE-ACSpatients.2. Prognostic value of isolated CK-MB~+ is equal to isolated cTnI~+when the tests performed early after admission (＜36h).3. cTnI is considered as both a biomarker of cardiac injury and anindex for the severity of left ventricular systolic function.4. Poor coronary angiographic and prognostic results seem to beassociated with elevated cTnI level and increased incidence of MACE.5. The relationship between proteinuria and elevated level of cTnI isstill not very clear. Slight renal dysfunction does not affect the result ofcTnI in MI.6. WBC count is of clinical importance in risk stratification of ACSpatients.Recognition of these risk differences may contribute to moreappropriate early use of antithrombotic therapy and invasive managementfor all cTn~+ patients.更多还原